WO2021121367A1 - Kras mutant protein inhibitors - Google Patents

Kras mutant protein inhibitors Download PDF

Info

Publication number
WO2021121367A1
WO2021121367A1 PCT/CN2020/137497 CN2020137497W WO2021121367A1 WO 2021121367 A1 WO2021121367 A1 WO 2021121367A1 CN 2020137497 W CN2020137497 W CN 2020137497W WO 2021121367 A1 WO2021121367 A1 WO 2021121367A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
pharmaceutically acceptable
acceptable salt
atropisomer
stereoisomer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2020/137497
Other languages
English (en)
French (fr)
Inventor
Amin LI
Sujing LI
Peng Wang
Chaojie DANG
Dan Liu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jacobio Pharmaceuticals Co Ltd
Original Assignee
Jacobio Pharmaceuticals Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to CR20220351A priority Critical patent/CR20220351A/es
Priority to BR112022011421A priority patent/BR112022011421A2/pt
Priority to CN202210597916.4A priority patent/CN115192577B/zh
Priority to JP2022537297A priority patent/JP7644517B2/ja
Priority to CN202111617953.9A priority patent/CN114349750A/zh
Priority to PH1/2022/551503A priority patent/PH12022551503A1/en
Priority to AU2020404319A priority patent/AU2020404319B2/en
Priority to EP20903388.5A priority patent/EP4077326A4/en
Priority to PE2022001137A priority patent/PE20230161A1/es
Priority to CN202111058976.0A priority patent/CN113651814B/zh
Priority to MX2022007527A priority patent/MX2022007527A/es
Priority to CN202080014581.8A priority patent/CN113454083A/zh
Application filed by Jacobio Pharmaceuticals Co Ltd filed Critical Jacobio Pharmaceuticals Co Ltd
Priority to IL293962A priority patent/IL293962B2/en
Priority to KR1020227024638A priority patent/KR102958327B1/ko
Priority to CA3165238A priority patent/CA3165238A1/en
Priority to US17/197,095 priority patent/US11180506B2/en
Publication of WO2021121367A1 publication Critical patent/WO2021121367A1/en
Priority to US17/407,418 priority patent/US11787811B2/en
Priority to US17/562,492 priority patent/US12195473B2/en
Anticipated expiration legal-status Critical
Priority to ZA2022/07450A priority patent/ZA202207450B/en
Priority to CONC2022/0010098A priority patent/CO2022010098A2/es
Ceased legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • Each n1, n2, n3, n4 or n5 at each occurrence is independently selected from 0, 1, 2, 3, 4, 5 or 6, provided that n1 and n2 is not 0 at the same time, n3 and n4 is not 0 at the same time;
  • R a or R b is independently selected from hydrogen or -C 1-6 alkyl
  • R 4 is each hydrogen in the is independently optionally substituted with 1R 42 , 2R 42 , 3R 42 , 4R 42 , 5R 42 or 6 R 42 ;
  • R 21 is selected from hydrogen; -F; -Cl; -Br; -C 1-3 alkyl; -C 1-3 alkyl substituted with -F or -Cl; -C 2-3 alkenyl; or-C 3-6 carbocyclic.
  • n2 is selected from 1 or 2.
  • R 4 is each hydrogen in the is independently optionally substituted with 1R 42 or 2R 42 .
  • alkylene means a difunctional group obtained by removal of a hydrogen atom from an alkyl group that is defined above.
  • methylene i.e., -CH 2 -
  • ethylene i.e., -CH 2 -CH 2 -or -CH (CH 3 ) -
  • propylene i.e., -CH 2 -CH 2 -CH 2 -, -CH (-CH 2 -CH 3 ) -or -CH 2 -CH (CH 3 ) -
  • Figure 3 is the graph of unit cell structure of single crystal diffraction for Compound 1-2;
  • Compound 1-2 was taken into a glass vial and dissolved with 0.8 mL ethanol and 0.4 mL n-heptane. The clear solution was evaporated to dryness at room temperature through a small hole to obtain the bulk-like crystals as the sample of the testing of single crystal diffraction using the following instrument and parameters in Table 2:
  • Compound 1, Compound 11, Compound 13 and Compound 14 have excellent pharmacokinetic properties (such as the higher C max and AUC) in mouse model comparative with the Compound A, Amgen 6 and Amgen 6.3, which make them more suitable for treating cancers with KRAS G12C mutation as an orally therapeutic active ingredient in clinic.
  • mice were treated with 400mg/kg compound 1-2 (po, QD) for 22 days, and mice body weight was measured twice a week during treatment.
  • the weight of mice varies with the number of days after cell inoculation is shown in Figure 9. From Figure 9, it can be seen that the Compound 1-2 have good safety.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Peptides Or Proteins (AREA)
PCT/CN2020/137497 2019-12-19 2020-12-18 Kras mutant protein inhibitors Ceased WO2021121367A1 (en)

Priority Applications (20)

Application Number Priority Date Filing Date Title
MX2022007527A MX2022007527A (es) 2019-12-19 2020-12-18 Inhibidores de proteinas kras mutantes.
CN202210597916.4A CN115192577B (zh) 2019-12-19 2020-12-18 Kras突变蛋白抑制剂
JP2022537297A JP7644517B2 (ja) 2019-12-19 2020-12-18 Ｋｒａｓ突然変異型タンパク質阻害剤
CN202111617953.9A CN114349750A (zh) 2019-12-19 2020-12-18 Kras突变蛋白抑制剂
PH1/2022/551503A PH12022551503A1 (en) 2019-12-19 2020-12-18 Kras mutant protein inhibitors
BR112022011421A BR112022011421A2 (pt) 2019-12-19 2020-12-18 Inibidores da proteína mutante kras
EP20903388.5A EP4077326A4 (en) 2019-12-19 2020-12-18 KRAS MUTANT PROTEIN INHIBITORS
PE2022001137A PE20230161A1 (es) 2019-12-19 2020-12-18 Inhibidores de proteinas kras mutantes
CN202111058976.0A CN113651814B (zh) 2019-12-19 2020-12-18 Kras突变蛋白抑制剂
CN202080014581.8A CN113454083A (zh) 2019-12-19 2020-12-18 Kras突变蛋白抑制剂
AU2020404319A AU2020404319B2 (en) 2019-12-19 2020-12-18 KRAS mutant protein inhibitors
CR20220351A CR20220351A (es) 2019-12-19 2020-12-18 Inhibidores de proteínas kras mutantes
IL293962A IL293962B2 (en) 2019-12-19 2020-12-18 Mutant KRAS protein inhibitors
KR1020227024638A KR102958327B1 (ko) 2019-12-19 2020-12-18 Kras 돌연변이체 단백질 억제제
CA3165238A CA3165238A1 (en) 2019-12-19 2020-12-18 Kras mutant protein inhibitors
US17/197,095 US11180506B2 (en) 2019-12-19 2021-03-10 KRAS mutant protein inhibitors
US17/407,418 US11787811B2 (en) 2019-12-19 2021-08-20 KRAS mutant protein inhibitors
US17/562,492 US12195473B2 (en) 2019-12-19 2021-12-27 KRAS mutant protein inhibitors
ZA2022/07450A ZA202207450B (en) 2019-12-19 2022-07-05 Kras mutant protein inhibitors
CONC2022/0010098A CO2022010098A2 (es) 2019-12-19 2022-07-18 Inhibidores de proteínas kras mutantes

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
CNPCT/CN2019/126687 2019-12-19
CN2019126687 2019-12-19
CN2020070885 2020-01-08
CNPCT/CN2020/070885 2020-01-08
CNPCT/CN2020/073723 2020-01-22
CN2020073723 2020-01-22
CNPCT/CN2020/078565 2020-03-10
CN2020078565 2020-03-10

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US17/197,095 Continuation US11180506B2 (en) 2019-12-19 2021-03-10 KRAS mutant protein inhibitors

Publications (1)

Publication Number Publication Date
WO2021121367A1 true WO2021121367A1 (en) 2021-06-24

Family

ID=76478185

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2020/137497 Ceased WO2021121367A1 (en) 2019-12-19 2020-12-18 Kras mutant protein inhibitors

Country Status (17)

Country Link
US (3) US11180506B2 (https=)
EP (1) EP4077326A4 (https=)
JP (1) JP7644517B2 (https=)
CN (4) CN114349750A (https=)
AU (1) AU2020404319B2 (https=)
BR (1) BR112022011421A2 (https=)
CA (1) CA3165238A1 (https=)
CL (1) CL2022001670A1 (https=)
CO (1) CO2022010098A2 (https=)
CR (1) CR20220351A (https=)
IL (1) IL293962B2 (https=)
MX (1) MX2022007527A (https=)
PE (1) PE20230161A1 (https=)
PH (1) PH12022551503A1 (https=)
TW (1) TWI871397B (https=)
WO (1) WO2021121367A1 (https=)
ZA (2) ZA202207450B (https=)

Cited By (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021249563A1 (zh) * 2020-06-12 2021-12-16 苏州泽璟生物制药股份有限公司 芳基或杂芳基并吡啶酮或嘧啶酮类衍生物及其制备方法和应用
EP3919483A4 (en) * 2019-01-29 2022-02-09 Brightgene Bio-medical Technology Co., Ltd. HETEROCYCLIC BENZOPYRIDONE COMPOUND AND USE THEREOF
WO2022060836A1 (en) 2020-09-15 2022-03-24 Revolution Medicines, Inc. Indole derivatives as ras inhibitors in the treatment of cancer
WO2022060583A1 (en) 2020-09-03 2022-03-24 Revolution Medicines, Inc. Use of sos1 inhibitors to treat malignancies with shp2 mutations
WO2022135591A1 (zh) * 2020-12-25 2022-06-30 苏州泽璟生物制药股份有限公司 芳基或杂芳基并吡啶酮或嘧啶酮类衍生物及其制备方法和应用
US11453683B1 (en) 2019-08-29 2022-09-27 Mirati Therapeutics, Inc. KRas G12D inhibitors
WO2022235864A1 (en) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Ras inhibitors
WO2022235870A1 (en) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Ras inhibitors for the treatment of cancer
US11548888B2 (en) 2019-01-10 2023-01-10 Mirati Therapeutics, Inc. KRas G12C inhibitors
WO2023008462A1 (ja) 2021-07-27 2023-02-02 東レ株式会社 癌の治療及び／又は予防のための医薬品
WO2023060253A1 (en) 2021-10-08 2023-04-13 Revolution Medicines, Inc. Ras inhibitors
WO2023114954A1 (en) 2021-12-17 2023-06-22 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
US11697657B2 (en) 2019-10-28 2023-07-11 Merck Sharp & Dohme Llc Small molecule inhibitors of KRAS G12C mutant
US11702418B2 (en) 2019-12-20 2023-07-18 Mirati Therapeutics, Inc. SOS1 inhibitors
EP4227307A1 (en) 2022-02-11 2023-08-16 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
WO2023172940A1 (en) 2022-03-08 2023-09-14 Revolution Medicines, Inc. Methods for treating immune refractory lung cancer
WO2023240263A1 (en) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Macrocyclic ras inhibitors
US11845761B2 (en) 2020-12-18 2023-12-19 Erasca, Inc. Tricyclic pyridones and pyrimidones
US11890285B2 (en) 2019-09-24 2024-02-06 Mirati Therapeutics, Inc. Combination therapies
US11932633B2 (en) 2018-05-07 2024-03-19 Mirati Therapeutics, Inc. KRas G12C inhibitors
WO2024081674A1 (en) 2022-10-11 2024-04-18 Aadi Bioscience, Inc. Combination therapies for the treatment of cancer
WO2024102421A2 (en) 2022-11-09 2024-05-16 Revolution Medicines, Inc. Compounds, complexes, and methods for their preparation and of their use
US12065430B2 (en) 2018-10-26 2024-08-20 Taiho Pharmaceutical Co., Ltd. Indazole compound or salt thereof
WO2024206858A1 (en) 2023-03-30 2024-10-03 Revolution Medicines, Inc. Compositions for inducing ras gtp hydrolysis and uses thereof
WO2024211663A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors
WO2024211712A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors
WO2024216048A1 (en) 2023-04-14 2024-10-17 Revolution Medicines, Inc. Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof
WO2024216016A1 (en) 2023-04-14 2024-10-17 Revolution Medicines, Inc. Crystalline forms of a ras inhibitor
US12122787B2 (en) 2019-09-20 2024-10-22 Shanghai Jemincare Pharmaceuticals Co., Ltd Fused pyridone compound, and preparation method therefor and use thereof
WO2024229406A1 (en) 2023-05-04 2024-11-07 Revolution Medicines, Inc. Combination therapy for a ras related disease or disorder
US12162893B2 (en) 2020-09-23 2024-12-10 Erasca, Inc. Tricyclic pyridones and pyrimidones
US12208099B2 (en) 2018-09-10 2025-01-28 Mirati Therapeutics, Inc. Combination therapies
WO2025034702A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Rmc-6291 for use in the treatment of ras protein-related disease or disorder
WO2025036470A1 (en) * 2023-08-17 2025-02-20 Jacobio Pharmaceuticals Co., Ltd. Use of compound a for treating a cancer
US12234245B2 (en) 2018-07-20 2025-02-25 Genentech, Inc. Sulfonimidamide compounds as inhibitors of interleukin-1 activity
WO2025067459A2 (en) 2023-09-29 2025-04-03 D3 Bio (Wuxi) Co., Ltd. Therapies for the treatment of cancer
WO2025080946A2 (en) 2023-10-12 2025-04-17 Revolution Medicines, Inc. Ras inhibitors
US12281113B2 (en) 2020-09-11 2025-04-22 Mirati Therapeutics, Inc. Crystalline forms of a KRas G12C inhibitor
US12336995B2 (en) 2018-09-10 2025-06-24 Mirati Therapeutics, Inc. Combination therapies
US12377101B2 (en) 2018-12-05 2025-08-05 Mirati Therapeutics, Inc. Combination therapies
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
US12398154B2 (en) 2020-12-15 2025-08-26 Mirati Therapeutics, Inc. Azaquinazoline pan-KRas inhibitors
US12421253B2 (en) 2020-12-16 2025-09-23 Mirati Therapeutics, Inc. Tetrahydropyridopyrimidine pan-KRas inhibitors
US12466840B2 (en) 2023-10-20 2025-11-11 Merck Sharp & Dohme Llc Small molecule inhibitors of KRAS proteins
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
US12479834B2 (en) 2019-11-29 2025-11-25 Taiho Pharmaceutical Co., Ltd. Phenol compound or salt thereof
US12485122B2 (en) 2018-09-10 2025-12-02 Mirati Therapeutics, Inc. Combination of palbociclib and adagrasib for lung cancer
WO2025255438A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en) 2024-06-28 2026-01-02 Revolution Medicines, Inc. Ras inhibitors
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
US12527795B2 (en) 2018-09-10 2026-01-20 Mirati Therapeutics, Inc. Compositions of adagrasib and mTOR inhibitors and methods of treatment therewith
WO2026050446A1 (en) 2024-08-29 2026-03-05 Revolution Medicines, Inc. Ras inhibitors
WO2026072904A2 (en) 2024-09-26 2026-04-02 Revolution Medicines, Inc. Compositions and methods for treating lung cancer
US12617802B2 (en) 2020-09-22 2026-05-05 Genentech, Inc. Sulfonimidamide compounds as NLRP3 modulators

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL312367A (en) 2017-01-31 2024-06-01 Arvinas Operations Inc Cereblon ligands and bifunctional compounds comprising the same
AU2020405129A1 (en) 2019-12-19 2022-06-23 Arvinas Operations, Inc. Compounds and methods for the targeted degradation of androgen receptor
IL293962B2 (en) * 2019-12-19 2025-10-01 Jacobio Pharmaceuticals Co Ltd Mutant KRAS protein inhibitors
CN115916778B (zh) * 2020-09-12 2026-03-20 赛诺哈勃药业（成都）有限公司 甲硫氨酸腺苷转移酶抑制剂、其制备方法及应用
CN117295742A (zh) * 2021-05-12 2023-12-26 北京加科思新药研发有限公司 化合物ⅰ的新形式及它们的应用
CN115894520A (zh) * 2021-09-23 2023-04-04 上海和誉生物医药科技有限公司 一种大环k-ras g12c抑制剂及其制备方法和在药学上的应用
CN121466307A (zh) * 2022-04-01 2026-02-06 劲方医药科技(上海)股份有限公司 药物组合物、其用途及癌症的治疗方法
WO2025036475A1 (en) * 2023-08-17 2025-02-20 Jacobio Pharmaceuticals Co., Ltd. A pharmaceutical combination and use thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110382482A (zh) 2017-01-26 2019-10-25 亚瑞克西斯制药公司 稠合的杂-杂二环化合物及其使用方法
US20190375749A1 (en) 2018-06-11 2019-12-12 Amgen Inc. Kras g12c inhibitors and methods of using the same
US20190374542A1 (en) 2018-06-12 2019-12-12 Amgen Inc. Kras g12c inhibitors and methods of using the same

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9078440B2 (en) 2010-12-16 2015-07-14 Bayer Intellectual Property Gmbh 6-(2-aminophenyl)picolinates and their use as herbicides
CA2922058A1 (en) 2013-10-18 2015-04-23 Medivation Technologies, Inc. Heterocyclic compounds and methods of use
US10892525B2 (en) 2016-06-29 2021-01-12 University Of Kentucky Research Foundation Rechargeable batteries including high-voltage cathode and redox shuttle conferring overcharge protection
WO2018064510A1 (en) * 2016-09-29 2018-04-05 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins
AU2018273356B2 (en) * 2017-05-22 2021-09-16 Amgen Inc. KRAS G12C inhibitors and methods of using the same
LT3710439T (lt) * 2017-11-15 2023-05-10 Mirati Therapeutics, Inc. Kras g12c inhibitoriai
EP3842433B1 (en) * 2018-01-19 2023-11-01 Medshine Discovery Inc. Pyridone-pyrimidine derivative acting as krasg12c mutein inhibitor
IL293962B2 (en) * 2019-12-19 2025-10-01 Jacobio Pharmaceuticals Co Ltd Mutant KRAS protein inhibitors

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110382482A (zh) 2017-01-26 2019-10-25 亚瑞克西斯制药公司 稠合的杂-杂二环化合物及其使用方法
US20190375749A1 (en) 2018-06-11 2019-12-12 Amgen Inc. Kras g12c inhibitors and methods of using the same
US20190374542A1 (en) 2018-06-12 2019-12-12 Amgen Inc. Kras g12c inhibitors and methods of using the same

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BANERJEE SOUVIK ET AL., JOURNAL OF MEDICINAL CHEMISTRY, vol. 60, 10 February 2017 (2017-02-10), pages 1309 - 1324
BRAHAMAM PUJALA, ACS MED. CHEM. LETT., 28 October 2016 (2016-10-28), pages 1 - 42
OLAH G. A. ET AL.: "THE JOURNAL OF ORGANIC CHEMISTRY", vol. 58, 1 January 1993, AMERICAN CHEMICAL SOCIETY
See also references of EP4077326A4
ZIENKIEWICZ JÖZEF ET AL., THE JOURNAL OF ORGANIC CHEMISTRY, vol. 69, 9 March 2004 (2004-03-09), pages 2551 - 2561

Cited By (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11932633B2 (en) 2018-05-07 2024-03-19 Mirati Therapeutics, Inc. KRas G12C inhibitors
US12234245B2 (en) 2018-07-20 2025-02-25 Genentech, Inc. Sulfonimidamide compounds as inhibitors of interleukin-1 activity
US12527795B2 (en) 2018-09-10 2026-01-20 Mirati Therapeutics, Inc. Compositions of adagrasib and mTOR inhibitors and methods of treatment therewith
US12208099B2 (en) 2018-09-10 2025-01-28 Mirati Therapeutics, Inc. Combination therapies
US12336995B2 (en) 2018-09-10 2025-06-24 Mirati Therapeutics, Inc. Combination therapies
US12485122B2 (en) 2018-09-10 2025-12-02 Mirati Therapeutics, Inc. Combination of palbociclib and adagrasib for lung cancer
US12065430B2 (en) 2018-10-26 2024-08-20 Taiho Pharmaceutical Co., Ltd. Indazole compound or salt thereof
US12377101B2 (en) 2018-12-05 2025-08-05 Mirati Therapeutics, Inc. Combination therapies
US11548888B2 (en) 2019-01-10 2023-01-10 Mirati Therapeutics, Inc. KRas G12C inhibitors
EP3919483A4 (en) * 2019-01-29 2022-02-09 Brightgene Bio-medical Technology Co., Ltd. HETEROCYCLIC BENZOPYRIDONE COMPOUND AND USE THEREOF
US11453683B1 (en) 2019-08-29 2022-09-27 Mirati Therapeutics, Inc. KRas G12D inhibitors
US11964989B2 (en) 2019-08-29 2024-04-23 Mirati Therapeutics, Inc. KRas G12D inhibitors
US12122787B2 (en) 2019-09-20 2024-10-22 Shanghai Jemincare Pharmaceuticals Co., Ltd Fused pyridone compound, and preparation method therefor and use thereof
US11890285B2 (en) 2019-09-24 2024-02-06 Mirati Therapeutics, Inc. Combination therapies
US12297208B2 (en) 2019-10-28 2025-05-13 Merck Sharp & Dohme Llc Small molecule inhibitors of KRAS G12C mutant
US12291538B2 (en) 2019-10-28 2025-05-06 Merck Sharp & Dohme Llc Small molecule inhibitors of KRAS G12C mutant
US11697657B2 (en) 2019-10-28 2023-07-11 Merck Sharp & Dohme Llc Small molecule inhibitors of KRAS G12C mutant
US12479834B2 (en) 2019-11-29 2025-11-25 Taiho Pharmaceutical Co., Ltd. Phenol compound or salt thereof
US12304915B2 (en) 2019-12-20 2025-05-20 Mirati Therapeutics, Inc. SOS1 inhibitors
US11702418B2 (en) 2019-12-20 2023-07-18 Mirati Therapeutics, Inc. SOS1 inhibitors
WO2021249563A1 (zh) * 2020-06-12 2021-12-16 苏州泽璟生物制药股份有限公司 芳基或杂芳基并吡啶酮或嘧啶酮类衍生物及其制备方法和应用
WO2022060583A1 (en) 2020-09-03 2022-03-24 Revolution Medicines, Inc. Use of sos1 inhibitors to treat malignancies with shp2 mutations
US12286431B2 (en) 2020-09-11 2025-04-29 Mirati Therapeutics, Inc. Crystalline forms of a KRas G12C inhibitor
US12281113B2 (en) 2020-09-11 2025-04-22 Mirati Therapeutics, Inc. Crystalline forms of a KRas G12C inhibitor
WO2022060836A1 (en) 2020-09-15 2022-03-24 Revolution Medicines, Inc. Indole derivatives as ras inhibitors in the treatment of cancer
US12617802B2 (en) 2020-09-22 2026-05-05 Genentech, Inc. Sulfonimidamide compounds as NLRP3 modulators
US12162893B2 (en) 2020-09-23 2024-12-10 Erasca, Inc. Tricyclic pyridones and pyrimidones
US12398154B2 (en) 2020-12-15 2025-08-26 Mirati Therapeutics, Inc. Azaquinazoline pan-KRas inhibitors
US12421253B2 (en) 2020-12-16 2025-09-23 Mirati Therapeutics, Inc. Tetrahydropyridopyrimidine pan-KRas inhibitors
US11845761B2 (en) 2020-12-18 2023-12-19 Erasca, Inc. Tricyclic pyridones and pyrimidones
WO2022135591A1 (zh) * 2020-12-25 2022-06-30 苏州泽璟生物制药股份有限公司 芳基或杂芳基并吡啶酮或嘧啶酮类衍生物及其制备方法和应用
WO2022235870A1 (en) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Ras inhibitors for the treatment of cancer
WO2022235864A1 (en) 2021-05-05 2022-11-10 Revolution Medicines, Inc. Ras inhibitors
WO2023008462A1 (ja) 2021-07-27 2023-02-02 東レ株式会社 癌の治療及び／又は予防のための医薬品
WO2023060253A1 (en) 2021-10-08 2023-04-13 Revolution Medicines, Inc. Ras inhibitors
WO2023114954A1 (en) 2021-12-17 2023-06-22 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
EP4227307A1 (en) 2022-02-11 2023-08-16 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
WO2023172940A1 (en) 2022-03-08 2023-09-14 Revolution Medicines, Inc. Methods for treating immune refractory lung cancer
WO2023240263A1 (en) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Macrocyclic ras inhibitors
WO2024081674A1 (en) 2022-10-11 2024-04-18 Aadi Bioscience, Inc. Combination therapies for the treatment of cancer
WO2024102421A2 (en) 2022-11-09 2024-05-16 Revolution Medicines, Inc. Compounds, complexes, and methods for their preparation and of their use
WO2024206858A1 (en) 2023-03-30 2024-10-03 Revolution Medicines, Inc. Compositions for inducing ras gtp hydrolysis and uses thereof
WO2024211663A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors
WO2024211712A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors
WO2024216016A1 (en) 2023-04-14 2024-10-17 Revolution Medicines, Inc. Crystalline forms of a ras inhibitor
WO2024216048A1 (en) 2023-04-14 2024-10-17 Revolution Medicines, Inc. Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof
WO2024229406A1 (en) 2023-05-04 2024-11-07 Revolution Medicines, Inc. Combination therapy for a ras related disease or disorder
WO2025034702A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Rmc-6291 for use in the treatment of ras protein-related disease or disorder
WO2025036470A1 (en) * 2023-08-17 2025-02-20 Jacobio Pharmaceuticals Co., Ltd. Use of compound a for treating a cancer
WO2025067459A2 (en) 2023-09-29 2025-04-03 D3 Bio (Wuxi) Co., Ltd. Therapies for the treatment of cancer
WO2025080946A2 (en) 2023-10-12 2025-04-17 Revolution Medicines, Inc. Ras inhibitors
US12466840B2 (en) 2023-10-20 2025-11-11 Merck Sharp & Dohme Llc Small molecule inhibitors of KRAS proteins
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
WO2025255438A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en) 2024-06-28 2026-01-02 Revolution Medicines, Inc. Ras inhibitors
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer
WO2026050446A1 (en) 2024-08-29 2026-03-05 Revolution Medicines, Inc. Ras inhibitors
WO2026072904A2 (en) 2024-09-26 2026-04-02 Revolution Medicines, Inc. Compositions and methods for treating lung cancer

Also Published As

Publication number Publication date
JP2023506532A (ja) 2023-02-16
ZA202207450B (en) 2023-04-26
IL293962B1 (en) 2025-06-01
US20230011726A1 (en) 2023-01-12
US11787811B2 (en) 2023-10-17
CR20220351A (es) 2022-10-31
MX2022007527A (es) 2022-07-19
CN115192577A (zh) 2022-10-18
CL2022001670A1 (es) 2023-03-17
CN113454083A (zh) 2021-09-28
JP7644517B2 (ja) 2025-03-12
CO2022010098A2 (es) 2022-10-11
AU2020404319A1 (en) 2022-08-18
IL293962B2 (en) 2025-10-01
CA3165238A1 (en) 2021-06-24
PH12022551503A1 (en) 2023-04-24
EP4077326A1 (en) 2022-10-26
PE20230161A1 (es) 2023-02-01
US20210292331A1 (en) 2021-09-23
US20220213109A1 (en) 2022-07-07
AU2020404319B2 (en) 2026-01-15
CN113651814B (zh) 2022-06-17
ZA202208783B (en) 2024-01-31
US11180506B2 (en) 2021-11-23
CN113651814A (zh) 2021-11-16
TWI871397B (zh) 2025-02-01
IL293962A (en) 2022-08-01
EP4077326A4 (en) 2024-04-24
CN114349750A (zh) 2022-04-15
BR112022011421A2 (pt) 2022-08-30
TW202128691A (zh) 2021-08-01
KR20220119088A (ko) 2022-08-26
US12195473B2 (en) 2025-01-14
CN115192577B (zh) 2024-03-29

Similar Documents

Publication Publication Date Title
WO2021121367A1 (en) Kras mutant protein inhibitors
WO2021185233A1 (en) Kras mutant protein inhibitors
WO2021088458A1 (en) Kras mutant protein inhibitor
CN116249683A (zh) 氘甲基取代吡嗪并吡嗪并喹啉酮类衍生物、其制备方法及其在医药上的应用
CN115304602A (zh) 吡嗪并吡嗪并萘啶二酮类衍生物、其制备方法及其医药上的用途
CN115557949A (zh) 四环类衍生物、其制备方法及其在医药上的应用
EP3889150A1 (en) Compound serving as irak inhibitor
US9724331B2 (en) Use of maleimide derivatives for preventing and treating leukemia
CN116157400A (zh) 杂环类衍生物及其制备方法和用途
WO2022227987A1 (zh) 杂环类衍生物及其制备方法和用途
EP4378943A1 (en) 8-oxo-3-azabicyclo[3.2.1]octane compound or salt thereof, and preparation method therefor and use thereof
CN117916234A (zh) 作为tyk2/jak1假激酶结构域抑制剂的化合物及合成和使用方法
KR102958327B1 (ko) Kras 돌연변이체 단백질 억제제
CA3066011A1 (en) Carboxylic acid derivatives as protein kinase inhibitors
EA047866B1 (ru) Ингибиторы мутантных белков kras
HK40065459A (en) Kras mutant protein inhibitors
HK40052926A (en) Kras mutant protein inhibitors
HK40052926B (en) Kras mutant protein inhibitors
WO2024227026A1 (en) Heterocyclic compounds as parp1 inhibitors
HK40051466A (en) Kras mutant protein inhibitors

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 20903388

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2022537297

Country of ref document: JP

Kind code of ref document: A

Ref document number: 3165238

Country of ref document: CA

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112022011421

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 20227024638

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: DZP2022000500

Country of ref document: DZ

Ref document number: NC2022/0010098

Country of ref document: CO

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2020903388

Country of ref document: EP

Effective date: 20220719

ENP Entry into the national phase

Ref document number: 2020404319

Country of ref document: AU

Date of ref document: 20201218

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 112022011421

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20220610

WWP Wipo information: published in national office

Ref document number: NC2022/0010098

Country of ref document: CO